Fungi infecting plants are evolving continuously into resistant strains, i.e. strains resistant to currently commercially available fungicides. This is of critical economic importance to farmers, grain supply and export trade and to the agrochemical industry and does negatively impact them. Fungi and other infective organisms affect all crops, not only affecting yield of crops, but also causing crop failures. It is generally opined that yield of crops up to the extent of 20% may be affected by fungal infestations to crops.
Several groups of chemical compounds as well as products derived or isolated from natural resources are commercially in use as fungicides. Other traditional techniques such as crop rotation are also continuously explored to overcome this menace. At present it costs around £200 million and takes more than ten years to develop and introduce new crop protection products. At the same time, focus is also on areas such as greater understanding of genetics and molecular biology of resistance mechanisms, molecular diagnostics for early warning of resistance development, improved risk assessment translating into guidance on doses, timings, mixtures etc.
Article titled “Synthesis and fungicidal activities of silicon-containing derivatives of 2-Aryl-3-(1H-1,2,4-triazol-1-yl)propanenitriles” by H Itoh et al. published in Chem Pharm Bull, 2001 July; 49(7); 909-11 reports a new series of silicon-containing derivatives of 2-aryl-3-(1H-1,2,4-triazol-1-yl)propanenitriles synthesized and evaluated for fungicidal activities against rice sheath blight and powdery mildew on cucumber. These derivatives exhibited higher efficacy than reference fungicides. CA1086734A1 discloses new and valuable morpholine derivatives and salts thereof, having a good fungicidal action, fungicides containing these compounds as active ingredients, and processes for combatting fungi with these compounds.
U.S. Pat. No. 4,530,922A discloses silicon-containing triazoles and imidazoles such as allyl[bis(4-fluorophenyl)](1H-1,2,4-triazol-1-ylmethyl) silane, and their use in controlling fungal diseases of living plants.
U.S. Pat. No. 4,579,842A discloses novel organosilyl compounds of the general formula gi below
where R1, R2 and R3 are alkyl, substituted alkyl, alkenyl, alkynyl, cycloalkyl, phenyl or substituted aryl, R4 and R5 are alkyl or hydrogen and Y is CH2, oxygen, nitrogen or alkyl-substituted nitrogen, their salts and fungicides containing these compounds.
EP0609099B1 discloses antimicrobial and antifungal compositions for use in agriculture and horticulture, and which contain at least one 3-(1,2,4-triazol-1-yi or imidazol-1-yl)-2-hydroxy-2-(optionally substituted phenyl)-1-(trisubstituted silyl) propane derivative together with at least one further antifungal and/or antimicrobial compound.
Article titled “Short chemoenzymatic synthesis of S-enantiomers of two systemic fungicides” by M Majerić et al. published in Biotechnology Letters, November 1995, Volume 17, Issue 11, pp 1189-1194 reports the S-enantiomers of fenpropidine and fenpropimorph, commercially important systemic fungicides. The process comprises 2-Methyl-(4′-tert-butyl) cinnamaldehyde (1) reduced by Saccharomyces cerevisiae (baker's yeast) to S-3-(4′-tert-butyl)-phenyl-2-propanol (4) in high chemical and very high optical yield (e.e. ≥99%). Chlorination of 4 to 5, and alkylation of the corresponding cyclic amines complete this short enantioselective synthesis of S-1-(1′-pyperidino)-2-methyl-3-(4′tert-butyl)-phenyl-propane (6) and S-1-(1′-(3′,5′-cisdimethyl)morpholino)-2-methyl-3-(4′-tert-butyl)-phenyl-propane (7).
Therefore, an approach that may be adopted is to study the currently available options and examine as to how they may be improved or their fungicidal action enhanced. This will not only provide more alternatives to currently commercialized products, but also reduce cost and time to develop and commercialise improved options to tackle resistance.
Accordingly, the present invention provides novel antifungal agents.